S231: PRIMARY MEDIASTINAL B-CELL LYMPHOMA HAVE A SUPERIOR OUTCOME COMPARED TO DIFFUSE LARGE-B-CELL LYMPHOMA TREATED WITH AXICABTAGENE CILOLEUCEL IN THE CART-SIE REAL LIFE ITALIAN STUDY
Authors: Annalisa Chiappella, Anna Dodero, Anna Guidetti, Silva Ljevar, Martina Pennisi, Beatrice Casadei, Eugenio Galli, Alice DI Rocco, Ilaria Cutini, Anna Maria Barbui, Stefania Bramanti, Maurizio Musso, Maria Chiara Tisi, Matteo Giovanni Carrabba, Massimo Martino, Mirko Farina, Barbara Botto, Giovanni Grillo, Marco Ladetto, Jacopo Olivieri, Luca Arcaini, Anisa Bermema, Rosalba Miceli, Patrizia Chiusolo, Pier Luigi Zinzani, Paolo Corradini
Journal: HemaSphere (2023)

Background: Axicabtagene ciloleucel (axi-cel) is reimbursed in Italy for the treatment of relapsed/refractory (R/R) large B-cell lymphoma (DLBCL), including diffuse large B-cell lymphoma (DLBCL-NOS), high grade B-cell lymphoma (HGBCL), transformed follicular lymphoma (tFL), and primary mediastinal B-cell lymphoma (PMBCL) patients, after at least two treatment lines, with an ECOG 0-1, and an upper age limit of 75 years. Aims: The aim of this analysis was to compare the outcome of PMBCL and DLBCL treated with axi-cel in the CART-SIE real life Italian study. Methods: The CART-SIE is an ongoing prospective and retrospective observational study collecting data on the outcome of all consecutive lymphoma patients treated with CAR-T cells in the italian centers. Results: From March 2019 to December 2022, 499 patients were enrolled and leukapheresed; 444 patients were infused (89%) and 426 with adequate follow-up were included into this analysis. Axi-cel was infused in 192 patients that were included in the present analysis, 57 PMBCL and 135 aggressive NHL (DLBCL), including DLBCL-NOS (85), HGBCL(28) and tFL (22), respectively. The clinical patient characteristics are reported in table 1; in summary, PMBCL patients presented a higher percentage of bulky, limited stage and primary refractory disease when compared to the DLBCL cohort. Bridging therapy was delivered to 47 out of 57 (83%) PMBCL patients and 103 out of 135 (76%) DLBCL (p=0.4455). Median follow-up time for infused patients was 10.99 months (IQR 4.18, 18.03). The Overall Response Rate (ORR, complete CR + partial PR response) at 30-days after the infusion was 44 out of 57 (77%) with 30 (53%) CR in PMBCL, and 97 out of 135 (72%) with 67 (50%) CR in DLBCL, (p=0.4206). The 12-months Overall Survival (OS) was 89% (95% CI: 81-98) in PMBCL versus 70% (95% CI: 62-80) in DLBCL (log-rank p=0.0016). Considering the different histology subtypes, the 12-months OS was 89% (95% CI: 81-98) in PMBCL versus 74% (95% CI: 63-86) in DLBCL-NOS, 58% (95% CI: 41-81) in HGBCL, 76% (95% CI: 58-100) in tFL (log-rank p=0.0013). The 12-months PFS was 65% (95% CI: 53-80) in PMBCL versus 47% (95% CI: 39-57) in DLBCL (log-rank p=0.0160). Considering the different histology subtypes, the 12-months PFS was 65% (95% CI: 53-80) in PMBCL versus 40% (95% CI: 30-54) in DLBCL-NOS, 51% (95% CI: 35-75) in HGBCL, 65% (95% CI: 47-90) in tFL (log-rank p=0.0420). All grades CRS was observed in 49 out of 57 (86%) PMBCL and 118 out of 135 (87%) DLBCL patients, with 9 (16%) and 12 (9%) severe (grade 3-4) CRS, respectively; all grades ICANS was reported in 25 (44%) PMBCL patients and in 46 (34%) DLBCL, with 12 (21%) and 14 (10%) severe (grade 3-4) ICANS, respectively. Tocilizumab was administered in 41 (72%) PMBCL and in 90 (67%) DLBCL, and steroids in 20 (35%) PMBCL and in 36 (27%) DLBCL patients. Twelve (21%) PMBCL and 15 (11%) DLBCL patients, were admitted in the intensive care unit. Treatment related mortality was reported in 3 (5%) PMBCL and 3 (2%) DLBCL patients. In a multivariable model with all clinically important and unbalanced variables (histotypes, age, disease status, Ann Arbor stage, IPI, bulky disease, previous ASCT, bridging therapy), PMBCL maintained its significantly better prognosis as compared to DLBCL, for OS and for PFS. Summary/Conclusion: CART-SIE is the first real-life study comparing the outcome of patients affected by R/R PMBCL and large B-cell lymphoma treated with axi-cel. PMBCL patients had a superior OS and PFS compared to DLBCL, with a similar incidence of CRS and ICANS.Keywords: relapsed/refractory, CAR-T, Real world data, Diffuse large B cell lymphoma